INTERFERICUS: Impact of the Presence of Anti-interferon Autoantibodies on the Viral Load in Severe Respiratory Infections
Study Details
Study Description
Brief Summary
Type I interferons (IFN-I) production is induced by the detection of viral molecules, such as RNA or DNA viral strands, through pattern recognition receptors (PRR) present on many immune cell types. Despite a minimal concentration, IFN-I secretion activate the secretion, by neighbouring cells, of more than 700 proteins with antiviral properties (inhibition of viral replication, destabilization of virus membranes, etc.). IFN-I constitute therefore one of the major first line of defence established by the immune system in response to viral infection. Briefly, during the Coronavirus disease (COVID-19) pandemic, several teams including ours, highlighted a lack of IFN-I response in approximately one in five individuals presenting a severe form of COVID-19.
Interestingly, within a large part of them, in vitro investigations revealed the presence of autoantibodies presenting neutralizing capacities against alpha and/or omega interferons This finding confirms the deleterious role of anti-IFN-I autoantibodies on the antiviral immune response and the key role of IFN-I pathway regarding defences against COVID-19 infection. Furthermore, those observations pave the way to interesting research that would allow understanding the underlying pathophysiological mechanisms of severe viral respiratory infection.
The research hypothesis are:
- IFN-I deficiency could induce severe forms of viral infections which could lead to intensive care admission ii) IFN-I deficiency could increase viral loads in nasopharyngeal samples, and be associated with protracted viral clearance iii) The frequency of viral co-infections may be higher in case of IFN-I antiviral pathway blockade, iv) severe forms of respiratory viruses' infections could be induced by other anti-cytokine autoantibodies.
In addition to confirming research hypotheses recently mentioned, the aim of this clinical protocol will be to assess the impact of antiviral innate immune response alterations in severe respiratory infections.
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Study Design
Outcome Measures
Primary Outcome Measures
- Change in viral load in nasopharyngeal samples [At Day 0 and Day 7]
Main outcome will be the difference of viral load (expressed in log copies per million cells) at D0±1 day and D7±1 day post inclusion (presence or absence of anti-IFN-I autoantibodies), and stratified by pathogen (influenza, respiratory syncytial virus (RSV), COVID-19).
Eligibility Criteria
Criteria
Inclusion Criteria:
- Patients with acute respiratory failure requiring the administration of oxygen* to maintain peripheral oxygen saturation at at least 90%
- in patients with chronic respiratory failure, an oxygen flow higher than the usual flow or a duration of non-invasive ventilation longer than the usual duration will be required.
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Patients with influenza, RSV or SARS-CoV-2 infection diagnosed by Reverse Transcription Polymerase Chain Reaction (RT-PCR) or antigen test in the last 7 days
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Patients hospitalized in participating intensive care units
Exclusion Criteria:
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Opposition of the patient or his close family/friend to inclusion in the study
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Patient under legal protection measure
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Patient who was included in this study during a previous stay
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Immunodepression defined by: bone marrow allograft less than 24 months old, chemotherapy for less than 6 months, HIV infection with CD4<200/mm3 or <15%, corticosteroid therapy for more than 2 weeks with a daily dose greater than 10 mg of prednisolone equivalent, immunosuppressive treatment administered in the previous 3 months (6 months for rituximab), aplasia, asplenia or splenectomy.
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Patient under 30 kg
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Hospices Civils de Lyon
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 69HCL22_0674